Research ProgramsOur research efforts are organized into four research programs, which serve to foster interactions and collaborations within specific themes. Cancer centermembers are affiliated with one program but work with collaborators from different programs in multidisciplinary groups.

The Chao Family Comprehensive Cancer Center's four research programs are:

Federal funding that maintains support for cancer center cores (and keeping prices low) depends critically on papers published that use our center facilities. As NIH transitions to digital, it becomes critically important that you list the support of the Cancer Center Support Grant (CCSG) in all appropriate publications. Verification of acknowledgment of support will come from electronically scanned publications. It is essential to cite the CCSG if your publication is cancer-related and supported by the center, such as: "Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number P30CA062203. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.”

Countdown to the CCSG Competing Application

days until the Cancer Center Support Grant (CCSG) competing application is due, Jan. 25, 2015.

Did You Know?

The BSR has instituted a policy of free collaboration on grant preparation for CFCCC members. This includes review for re-submissions when addressing criticism of original application. This effort is partially supported through the Cancer Center's P30 grant.

The Chao Family Comprehensive Cancer Center supports seven shared resources that provide services essential to basic and translational research. Each of these is available to researchers at UC Irvine and other institutions. Investigators do not have to be cancer center members to use the facilities. Each shared resource is partially funded by user fees and other support. To learn more about the services offered and how they might benefit your research, please refer to the specific contact information listed under the shared resource section of this newsletter or contact:

The goal of the BBSR is to support cancer researchers by providing them with the necessary expertise and assistance to incorporate patient/participant-reported outcomes (PROs), health-related quality-of-life (QOL) and counseling interventions. The BBSR participates in translational research in psychoneuroimmunology, examination of behavioral issues that enhance recruitment and compliance within cancer center clinical trials and development of behavioral and QOL outcomes associated with clinical trials. The primary activities of the BBSR include: consultation on behavioral and/or QOL self-report measurement, research design, data collection, interpretation of self-report data, manuscript preparation and counseling interventions within clinical trials.

Quarterly HighlightsOvarian cancer (OC) remains a major health problem in the United Sates. There is little genomic or biologic characterization of these tumors, or patient-reported outcomes that characterize long term (LT) survivors. The clinical importance of identifying subsets of patients who may or may not benefit from therapy, and understanding the biology of their tumors, is significant both from a patient survival and quality of life (QOL) standpoint. The characterization of LT survivors of advanced stage OC will potentially identify molecular and clinical pathways that can be targeted to help women who have shorter survivals. Further, careful characterization of these patients, including their initial and longitudinal health-related QOL reports, their response to treatments, and their tumors will provide significant measures of prognostic factors. The systematic molecular and patient-reported outcomes evaluation of LT survivors of OC (both early and advanced stage) will yield data, which can significantly impact the management of OC patients. Our aims will characterize the genomic, biologic, and biobehavioral basis for LT survivors of EOC. Additionally, BBSR will determine the extent to which health-related QOL measures, additional patient-reported outcomes (PROs), and key CTCAE criteria predict LT ovarian cancer survival, and further, we will examine as an exploratory aim, the potential relationship between health-related QOL, PROs, and key CTCAE criteria with genomic features predicting disease recurrence.

The mission of the BSR faculty and staff is to support the conception, design, implementation, analysis and reporting of research conducted by members of the Chao Family Comprehensive Cancer Center.

Quarterly HighlightsThe Biostatistics Shared Resource (BSR) recently collaborated with CFCCC members Dr. Robert Bristow (CPP) and Dr. Leslie Randall (SPT) on a phase I dose-finding study in the setting of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC). Briefly, HIPEC is the administration of one dose of heated intraperitoneal therapy at the time of standard cytoreductive surgery for gynecologic peritoneal surface malignancies. Bristow and Randall are leading researchers in the use of HIPEC, but to date, little empirical data is available on the maximally tolerated dose (MTD) of chemotherapy administered during the procedure. Guided by collaboration with the BSR, the phase I study will employ a continual reassessment method (CRM) for quantifying the MTD of chemotherapy during the HIPEC procedure. The proposed Bayesian adaptive design treats trial patients at the best guess of the MTD based on all cumulative observations combined with prior information elicited from HIPEC experts. The proposal also received CFCCC seed grant funding and the project has led to the submission of an NCI R21 statistical methods grant with Dan Gillen, PI (CPP), who will develop and investigate the above mentioned novel dose-finding methods, using the HIPEC trial as the primary motivating example.

The primary objective of the ETR is to provide basic, translational and clinical cancer center researchers access to, and analysis of, human and animal tissues.

Quarterly HighlightsIn the Marian Waterman (SPT) laboratory, the Experimental Tissue Resource (ETR) Core have been actively involved in the generation, propagation and tissue processing of xenograft and orthotopic tumor models of colon cancer in NSG mice, which is used in the analysis of the effects of modulating Wnt signaling on cancer cell glycolytic activity. Using Fluorescence Lifetime Intensity Microscopy imaging of live perfused tumors, they have demonstrated the regulation of aerobic glycolysis vs. oxidative phosphorylation by Wnt target genes. A revised manuscript is under review at EMBO. The ETR support was critical in this work, providing animal protocol consultation, histology services, immunohistochemical staining, and histopathology interpretive services.

The mission of the GHTF is to provide genome-wide analysis for clients interested in gene expression, regulation of gene expression and genome sequence and variation. The primary forms of genome-wide analysis are the Affymetrix GeneChip, Illumina HiSeq 2500 next-generation sequencing and PacBio RS real-time single molecule sequencing.

Quarterly HighlightsBogi Andersen’s (SPT) lab recently found that the circadian clock regulates circadian variation in cell proliferation in the epidermis and the sensitivity to UVB-induced DNA damage, the main carcinogen for skin, (Proc Natl Acad Sci 109(29):11758-11763; 2012). The gene expression profiling performed by the Genomics High Throughput Facility (GHTF) allowed the Andersen Lab to define the circadian transcriptome in skin and thereby the role in cell proliferation. The NIH grant supporting the project was recently renewed and Andersen is planning many experiments that require GHTF support.

The longterm goal of the IVFOI core is to promote the application of imaging techniques in cancer research. Toward this aim, the development and application of imaging technologies are key research areas. The current imaging facilities at the center include:

Quarterly HighlightsThe In-Vivo Functional Onco-Imaging (IVFOI) Facility has developed the world’s first MR compatible SPECT system for animal imaging studies. The Core collected preliminary data, using novel hybrid technology, and supported two recently awarded projects-including Drs. Randall (SPT) and Su (OIB): (1) Leslie Randall, PI. Funding Agency: The American Board of Obstetrics and Gynecology, “Preclinical Validation of 123I-Bevacizumab as a Potential Pharmacodynamic Marker of Vascular Endothelial Growth Factor Activity and Predictive Marker of Bevacizumab Response;” FY 2013 funding is $120,000, and (2) Lydia Su, PI. Funding Agency: NIH (R01CA127929), “Predicting Neoadjuvant Chemo Response/Prognosis Using Imaging Biomarkers;” total funding: $3,652,128. The preliminary data collected by IVFOI’s cutting-edge imaging technology played a critical role in the success of the applications. The IVFOI continues to support these grants through the acquisition of data using orthotopic ovarian cancer tumor modeling and by contributing to the development and testing of a breast imaging version of this hybrid technique.

The OBC
is comprised of three components: (1) The self-use facility located in 4443 McGaugh Hall at the UC Irvine Campus houses a Zeiss LSM 780 and a LSM 700 that can image live cells, fixed samples, model organisms, single molecules and anything in between. For example,a two photon laser is utilized for deep tissue imaging and single photon lasers for imaging all fluorophores from DAPI (405nm) to far red (633nm). The Fluorescence Lifetime Microscopy (FLIM) detector for studying molecules based on their fluorescence lifetime provides a way of studying metabolic states of cancer cells compared to normal cells. Volocity image analysis software is available on a high-end work station for use from an office computer. Training is provided and targeted workshops occur routinely. Users can sign up for time on the scopes 24 hours a day, 7 days a week. (2) The Laer Microbeam and Medical Program (LAMMP) facility located in the Beckman Laser Institute and Medical Clinic is available for collaborative use and protocol development using a number of microscopes. Information about the capabilities can be found at http://lammp.bli.uci.edu/. Some of their capabilities include Mobile Device Management (MDM) platforms for studying skin carcinomas and techniques to detect early melanoma non invasively. (3) A flow cytometry facility is available in Hewitt Hall and contains a MoFlo Cytomation and B-D FACScalibur cytometer. Contact information for the facility can be found at http://dbc.bio.uci.edu/FlowCytoHome.html.

Quarterly HighlightsDavid Fruman’s (SPT) lab has compared the efficacy of rapamycin to PP242, which is an inhibitor of the active site of mTOR, in models of acute leukemia harboring the Philadelphia chromosome translocation. OBC facilities helped demonstrate that PP242, but not rapamycin, causes death of mouse and human leukemia cells and that PP242 delays onset and augments the effect of current front-line tyrosine kinase inhibitors more effectively than rapamycin.

The TMF assists in the use of genetically-modified mice in biological and biomedical research. An important goal of the TMF is to identify new technology and methodology that is likely to benefit UC Irvine investigators using mice in their research programs and to import and provide such technology to UC Irvine investigators. The TMF makes investigators aware of new and existing developments via the TMF website, in seminars and lectures, via the UC Irvine mouse users email list and by word-of-mouth.

Quarterly HighlightsThe Transgenic Mouse Facility is assisting Dr. Richard Van Etten (SPT) with the relocation of multiple strains of genetically modified mice from Tufts University to UC Irvine. This process is complicated because of the difference in murine health status between the vivarium they are coming from and the animal rooms at UCI. As such, pathogen free (barrier) environments can reduce experimental variability that may arise from subclinical exposures that potentially mask an experimental outcome. For example, for each strain, the TMF superovulates several females and mates them to produce fertilized pre-implantation embryos that are harvested and transferred surgically to the reproductive tract of foster female mice. This process, known as rederivation, eliminates all known murine pathogens that are excluded from UCI colonies and will allow Van Etten to move his unique strains of genetically modified mice into a pathogen free animal facility at UC Irvine